Review Article
INTRODUCTION
There is rising attention in the world regarding natural product researches as plants are always known to be the traditional
source of medicine due to the presence of natural products with high chemical diversity. In natural system plants face a plethora
of antagonism and thus evolved myriad of defence mechanisms by which they are able to cope up with various kinds of biotic
and abiotic stresses. These large arrays of natural products, in concern here, are referred to as secondary metabolites as they
are not directly involved in growth, development and metabolism even though they are derived from primary metabolism. Apart
from combating stress, they also function as attractants due to the presence of compounds responsible for conferring bright
and attractive colour of fruits and flowers. In addition to their physiological roles in plants, they are also extensively exploited as
pharmaceuticals, food additives and cosmetic products. There are three major groups of secondary metabolites namely terpenes,
phenolics and N and S containing compound. Terpenes which are being composed of 5-C isopentanoid units are toxins and feeding
deterrents to many herbivores. Phenolics synthesized primarily shikimic acid pathway which have several important defensive
role in the plants. Members of the third major group which are basically nitrogen (N) and Sulphar(S) containing compounds are
synthesized principally from common amino acids [1]. Tea is one of the most popular beverages taken throughout the world is a
very good source of important secondary metabolites like monoterpenoids, carotenoids and catechins etc. Monoterpenoids and
carotenoids are most important constituents of tea aroma and flavor. The formation of tea aroma is because of the synthesis of
volatile monoterpenoids and carotenoids, while catechins are responsible for the beneficial health effects of tea.
Being the second most popular beverage in the world, tea drinking originated in China around 4000–5000 years ago. Today,
3 billion cups of tea are consumed everyday by millions of people all over the world. Now days, it is being cultivated in at least
30 countries around the world. All varieties and cultivars of the tea plant is the member to a single species, Camellia sinensis [2],
a member of Theaceae family, cultivated across the world inspecially in the tropical and subtropical regions. Tea beverage is an
infusion of the dried leaves of the plant. Tea is an evergreen shrub or that can grow to a height of almost 30 feet, but is usually
The natural polyphenols in green tea include epicatechin (EC), (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC),
(-)-epicatechin-3- gallate (ECG) (Figure 2). Other minor catechins present in tea including (+)-catechin (C), (+)-gallocatechin (GC),
(-)-gallocatechingallate (GCG), (-)-catechingallate (CG) [8]. Comparative antioxidant activities among tea catechins has been found to be
(-)-epigallocatechin-3-gallate EGCG = (-)-epicatechin-3-gallate (ECG) > (-)-epigallocatechin (EGC) > (-)-epicatechin (EC) [9]. Thus EGCG has
the highest concentration followed by EGC, ECG and EC in decreasing order [10]. Green tea catechins have been found to be more efficient
as radical scavengers than vitamin E and C [9,11] among them EGCG accounts for more than 10% of the extract dry weight [12]. Most of
the health benefits of green tea are mainly due to its antioxidant properties and in scavenging of reactive oxygen species, the ability
conferred by polyphenols and catechins [13]. These properties are attributed due to the property of the phenolic hydroxyl groups present
in the B-ring in ungalloylatedcatechins (EC and EGC) (Figure 3) and in the B- and D-rings of the galloylatedcatechins (ECG and EGCG) [14].
The antioxidant as well as radical scavenging properties are conferred by the presence of the 3,4,5-trihydroxy B-ring [9,15] Metal-chelation
property of green tea catechins are also significant contributors to their antioxidant property [16-18].
Another approach as remedies of Alzheimer’s is to inhibit AChE by different medicinal plant extracts. Plenty of methods
for reducing of AChE inhibitory activity from secondary metabolites of natural resources has been reported based on Ellman’s
reactions [96]. The TLC based bioautographic method developed by Marston et al. [97], Spectrophotometric study the thin-layer
chromatography method [98] and micro-plate assay [98,99] have been reported to be useful in studying AChE inhibiting activities.
Direct spectral analysis and studying enzyme kinetics in the presence and absence of the inhibitor can be another rapid approach.
Okello et al. [100] carried out an in vitro colorimetric assay from Ellman’s reactions [96] and reported that both green tea as well as
black tea reduced the activity of AChE in a dose dependent manner IC50value 0.003 ± 0.0004 mg/ml and 0.06 ± 0.005 mg/ml
respectively for green tea and black tea. So this study has proven green tea to be more effective than black tea in inhibiting AChE
enzyme. This study also revealed that green tea at a final assay concentration of 0.03 mg/ml reduced β-secretase by 27% after 5
min incubation, but after 60 min inhibition reached 38% and no further increase in the activity after 60 min incubation.
Preclinical Studies on EGCG Neuroprotective Mechanism of Action
Green tea has been shown to have significant preventive effect against age-associated neurodegenerative diseases [101].
Alzheimer's disease and Parkinson's disease are two common types of dementia related diseases that have been studied as
part of the effort to investigate the effect of green tea on neurodegenerative diseases, as its effects may be relatively exquisite,
therefore, it’s difficult to measure the benefits of green tea on brain function in healthy people quantitatively. A concern of
considerable research has been done to examine the possible effects of green tea in addition to slow down the effects of age
related dementia [102]. Alzheimer’s disease, the most common form of dementia in later life, where brain cells may have high
metabolic rate which in turn ended up in generation of reactive oxidative species. Oxidative damage to neuronal biomolecules and
increased aggregation of iron in specific brain areas are considered major pathological measures of Alzheimer’s disease [103].There
are studies on preventive effects of green tea catechins, in vitro as well as in vivo showed that both green tea extract and EGCG
having the potential in reducing mice striatal Acetylcholine depletion as well as in substantial nigra (SN) acetylcholine neuron
loss. Catechin containing compounds can be treated as potent radical anti-oxidants and ferric ion chelators. As transition metal
ions causes a wide range of neurodegenerative disorders including iron deposition in microglia of SN in Parkinsonism patients
[104-106]
thus polyphenolics are the main constituents behind the utility of green tea and EGCG against N-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP) created neurotoxicity [107]. The catechol structural resemblance inhibits [3H] AChE uptake by presynaptic
transporters thereby blocking 1-methyl-4-phenylpyridinium (MPP+) uptake through competition for the vesicular transporter and
protects neuronal injury [108]. In vitro studies proved that EGCG resists the activity of the enzyme catechol-O-methyltransferase
(COMT) as well as MPP+ and 6-hydroxydopamine (6-OHDA)-induced neurotoxicity [109,110].
In vitro observations showed that EGCG, also present in green tea helps to prevent amyloid beta peptides (Aβ)-induced
neurotoxicity [111], and EC can be used to reduce nascent Aβ fibrils, elongation of the(Aβ) fibrils and destabilization of the formation
of assemblies [112] in Alzheimer’s disease patients. It can regulate the proteolytic cleaving process of APP under in vivo and in
vitro conditions [92] as a result green tea polyphenols might be potent therapeutic agents for Parkinson's disease, as well as for
Alzheimer’s disease. Long term treatment of mice with EGCG promoted the non-amyloidogenic α-secretase pathway of APP in
neuronal cell cultures resulting in a momentous augment in soluble APPα (sAPPα) [92] in the hippocampus. In a recent study, EGCG
revealed to be promoted the generation of sAPPα by decreasing Aβ levels and plaques via the non-amyloidogenic α-secretase
proteolytic pathway [113,114]. Prophylactic benefits of long term consumption of EGCG studied on rat, found to be effective on
spatial cognitive learning impairment caused by Aβ cerebral ventricle infusion [115], as well as in prevention of lipopolysaccharide-
mediated neuronal cell death and memory impairment of mice, possibly as a result of reduction of Aβ levels via inhibition of β- and
γ-secretases [116,117].
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